Summary
The pharmacokinetics of phenytoin was studied in 66 epileptic Chinese children and adults. The data were analysed by the population approach, using the non-linear mixed effect model, in the MULTI (ELS) program. There was no age or gender-related effect on either the apparent maximum elimination rate (kmax) or Michaelis-Menten constant (KM). Kmax was related to body weight 0.656. The population pharmacokinetics was similar in children and adults. Kmax and KM were estimated to be 30.72 mg·kg−0.656 day−1 and 2.307 mg·l−1, respectively. Kmax was higher than reported values, and KM was comparable to that reported in a study in Japanese, but was much lower than that reported in studies of European patients. The inter-individual variability of KM (CV 65.58%) was substantially higher than that of kmax (CV 28.49%), and the residual (intra-individual) variability was found 21.33% (CV).
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Martin E, Tozer NT, Sheiner LB, Riegelman S (1977) The clinical pharmacokinetics of phenytoin. J Pharmacokinet Biopharm 5: 579–596
Vozeh S, Muir KT, Sheiner LB, Follath F (1981) Predicting individual phenytoin dosage. J Pharmacokinet Biopharm 9: 131–146
Yukawa E, Higuchi S, Aoyama T (1988) Evaluation of single-point phenytoin dosage prediction methods in pediatric patients. J Pharmacobiodynam 11. 736–743
Lee HS, Chan KY (1981) Phenytoin and phenobarbitone plasma level dose relationships in Chinese epileptic children in Singapore. Ther Drug Monit 3: 247–252
Yamaoka T, Tanaka H (1987) A new version of MULTI (ELS) for extended nonlinear least squares. J Pharmacobiodynam 10: 26–34
Sheiner LB, Beal SL (1980) Evaluation of methods for estimating population pharmacokinetic parameters. I. Michaelis-Menten model: Routine clinical pharmacokinetic data. J Pharmacokinet Biopharm 6: 553–571
Grasela TH, Sheiner LB, Rambeck B, Boenigk HE, Dunlop A, Mullen PW, Wadsworth J, Richens A, Ishizaki T, Chiba K, Miura H, Minagawa K, Blain PG, Mucklow JC, Bacon CT (1983) Steady-state pharmacokinetics of phenytoin from routinely collected patient data. Clin Pharmacokinet 8: 355–364
Vozeh S, Wenk M, Follath F (1984) 2. Experience with NON-MEM: Analysis of serum concentration data in patients treated with mexiletine and lidocaine. Drug Metabol Rev 15: 305–315
Yamaoka K, Tanaka H, Okumura K, Yasuhara M, Hori R (1986) An analysis program MULTI (ELS) based on extended nonlinear least square method for microcomputers. J Pharmacobiodynam 9: 161–173
Yamaoka K, Nakagawa T, Tanaka H, Yasuhara M, Okumura K, Hori R (1985) A nonlinear multiple regression program, MULTI2 (Bayes), based on Bayesian algorithm for microcomputers. J Pharmacobiodynam 8: 246–256
Sheiner LB, Beal SL (1981) Some suggestions for measuring predictive performance. J Pharmacokinet Biopharm 9: 503–512
Gugler R, Manion CV, Azarnoff DL (1976) Phenytoin: Pharmacokinetic and bioavailability. Clin Pharmacol Ther 19: 135–142
Rambeck B, Boenigk HE, Dunlop A, Mullen PW, Wadsworth J, Richens A (1979) Predicting phenytoin dose — a revised nomogram. Ther Drug Monit 1: 325–333
Chiba K, Ishizaki T, Miura H, Minagawa K (1980) Michaelis-Menten pharmacokinetics of diphenylhydantoin and application in the pediatric age patient. J Pediatr 96: 479–484
Blain PG, Mucklow JC, Bacon CJ, Rawlins MD (1981) Pharmacokinetics of phenytoin in children. Br J Clin Pharmacol 12: 659–661
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Chan, E., Ti, T.Y. & Lee, H.S. Population pharmacokinetics of phenytoin in Singapore Chinese. Eur J Clin Pharmacol 39, 177–181 (1990). https://doi.org/10.1007/BF00280055
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DOI: https://doi.org/10.1007/BF00280055